Exposure to Low Doses of Dechlorane Plus Promotes Adipose Tissue Dysfunction and Glucose Intolerance in Male Mice
- DOI
- Language of the publication
- English
- Date
- 2020-06-18
- Type
- Article
- Author(s)
- Peshdary, Vian
- Styles, George
- Rigden, Marc
- Caldwell, Don
- Alice Kawata, Alice
- Sorisky, Alexander
- Atlas, Ella
- Publisher
- Oxford University Press
Abstract
The prevalence of type 2 diabetes (T2D) continues to increase worldwide. It is well established that genetic susceptibility, obesity, overnutrition and a sedentary life style are risk factors for the development of T2D. However, more recently, studies have also proposed links between exposure to endocrine-disrupting chemicals (EDCs) and altered glucose metabolism. Human exposure to environmental pollutants that are suspected to have endocrine disruptor activity is ubiquitous. One such chemical is Dechlorane Plus (DP), a flame retardant, that is now detected in humans and the environment. Here we show that exposure of mice to low, environmentally relevant doses of DP promoted glucose intolerance in mice fed a high-fat diet independent of weight gain. Furthermore, DP had pronounced effects on the adipose tissue, where it induced the development of hypertrophied white adipose tissue (WAT), and increased serum levels of resistin, leptin, and plasminogen activator inhibitor-1. In addition, DP exposure induced “whitening” of brown adipose tissue (BAT), and reduced BAT uncoupling protein 1 expression. Importantly, some of these effects occurred even when the mice were fed a regular, low-fat, diet. Finally, WAT adipogenic markers were reduced with DP treatment in the WAT. We also show that DP directly inhibited insulin signaling in murine adipocytes and human primary subcutaneous adipocytes in vitro. Taken together, our results show that the exposure to low and environmentally relevant levels of DP may contribute to the development of T2D.
Plain language summary
Health Canada is responsible for the assessment and management of health risks to Canadians associated with exposure to products and chemicals in the environment. Health Canada conducted a study to investigate the effects of a flame retardant, to which Canadians are being exposed, on the development of metabolic disease such as diabetes. The prevalence of diabetes is a major health concern in Canada and the rest of the world. Diabetes is a disease where the tissues in the body become resistant to the hormone insulin, which regulates sugar (glucose) levels in the blood. The causes of diabetes include interactions between genetic background, obesity, lifestyle, and environmental factors. Studies have proposed links between exposure to environmental pollutants and the development of diabetes. The study conducted showed that exposure to environmentally relevant doses of the flame retardant, Dechlorane Plus (DP), detected in humans and the environment, impaired the ability of mice fed high fat diet (HFD) to clear glucose from the bloodstream. DP led to the development of fat tissue dysfunction and increased levels of markers associated with the development of diabetes. DP directly inhibited the action of insulin in mouse pre-fat cells as well as mature mouse and human fat cells. Taken together, our results show that the exposure to environmentally relevant levels of DP may contribute to the development of diabetes.
Subject
- Health,
- Health and safety